Correspondence

Persistent Carriage of Hepatitis E Virus in Patients with HIV Infection

N Engl J Med 2009; 361:1025-1027September 3, 2009

Article

To the Editor:

Hepatitis E virus is an emerging infection in developed countries, with many clinical manifestations.1 We describe a 48-year-old bisexual white male who was infected with human immunodeficiency virus type 1 (HIV-1) and who had elevated liver enzymes and infection with hepatitis E virus for at least 24 months. He had received a diagnosis of HIV infection in 2001 and was treated for tuberculosis in 2003. He had a 20-year history of excessive alcohol consumption (30 to 40 units [8 g of pure alcohol] per week) but reported never having injected drugs or received blood products. In January 2007, antiretroviral therapy was begun; the patient had a CD4 cell count of 30 per cubic millimeter and an HIV viral load of 8.3×10⁴ copies per milliliter. Other medications started were valganciclovir, co-trimoxazole, oxycodone, and diazepam. The alanine aminotransferase level was elevated (to 51 IU per liter), and the alkaline phosphatase and bilirubin levels were normal. The results of serologic testing for hepatitis A infection were consistent with a past infection; serologic tests for hepatitis B and C were negative, as were polymerase-chain-reaction (PCR) assays for hepatitis B and C and cytomegalovirus. Liver ultrasonography showed no evidence of parenchymal liver disease.

From March 2007 to January 2009, the patient's CD4 count remained under 200 cells per cubic millimeter, despite suppression of HIV replication starting in June 2007, and the alanine aminotransferase level remained abnormal, though he had reduced his alcohol consumption to 2 to 3 units weekly. Hepatitis E viral RNA was detected in serum and feces specimens, by means of PCR assay, in February 2009. Retrospective testing revealed the presence of hepatitis E virus in serum and feces samples that had been obtained during the preceding 18 months. Tests for hepatitis E virus were performed with the use of hepatitis E virus IgG and IgM enzyme immunoassay kits from two manufacturers: Beijing Wantai Biological Pharmacy Enterprise and Biokit. Wantai and Biokit test results were both positive for serum samples collected later during the 18-month period, whereas for samples collected earlier in the period, the Biokit results were negative but the Wantai tests were positive (Figure 1Figure 1Laboratory Data for a Patient with Coinfection with Human Immunodeficiency Virus (HIV) and Hepatitis E Virus (HEV).). Sequencing showed the hepatitis E virus to be genotype 3, which is predominant in developed countries.1 Liver biopsy performed in March 2009 revealed established cirrhosis with active inflammation.

Until recently, hepatitis E virus was considered to cause acute infection only.1 Chronic infection with hepatitis E virus, along with progressive liver disease, has now been described in recipients of solid-organ transplants2 and a patient with lymphoma3 who is receiving immunosuppressive therapy. Data for our patient show that chronic infection with hepatitis E virus may occur in patients with HIV infection and is associated with active hepatitis.

Coinfection with hepatitis E virus and HIV may be overlooked because drug-induced liver injury is common in patients receiving antiretroviral therapy.4 Therefore, infection with hepatitis E virus may be misdiagnosed as drug-induced liver injury.5 Serologic testing may be unreliable in this context; PCR-based detection of hepatitis E viral RNA is essential to make the diagnosis. The prevalence of coinfection with hepatitis E virus and HIV, and the effects of such coinfection on chronic liver disease and prolonged carriage and the excretion of the hepatitis E virus, should be investigated further.

Harry R. Dalton, F.R.C.P.
Richard P. Bendall, F.R.C.Path.
Frances E. Keane, F.R.C.P.
Royal Cornwall Hospital, Cornwall, United Kingdom
richard.bendall@rcht.cornwall.nhs.uk

Richard S. Tedder, F.R.C.Path.
Samreen Ijaz, Ph.D.
Health Protection Agency, London, United Kingdom

Supported in part by a grant from the Duchy Healthcare Charity.

Dr. Dalton reports receiving lecture fees from GlaxoSmithKline and Beijing Wantai Biological Pharmacy Enterprise. No other potential conflict of interest relevant to this letter was reported.

5 References

1. 1

   Dalton HR, Bendall R, Ijaz S, Banks M. Hepatitis E: an emerging infection in developed countries. Lancet Infect Dis 2008;8:698-709
   CrossRef | Web of Science | Medline

2. 2

   Kamar N, Selves J, Mansuy J-M, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med 2008;358:811-817
   Full Text | Web of Science | Medline

3. 3

   Ollier L, Tieulie N, Sanderson F, et al. Chronic hepatitis after hepatitis E virus infection in a patient with non-Hodgkin lymphoma taking rituximab. Ann Intern Med 2009;150:430-431
   Web of Science | Medline

4. 4

   Montessori V, Press N, Harris M, Akagi L, Montaner JS. Adverse effects of antiretroviral therapy for HIV infection. CMAJ 2004;170:229-238
   Web of Science | Medline

5. 5

   Dalton HR, Fellows HJ, Stableforth W, et al. The role of hepatitis E virus testing in drug-induced liver injury. Aliment Pharmacol Ther 2007;26:1429-1435
   CrossRef | Web of Science | Medline

Citing Articles (44)

Citing Articles

1. 1

   N.F. Crum-Cianflone, . (2012) Hepatitis E Virus Infection in HIV-infected Persons. Emerging Infectious Diseases 18:3,
   CrossRef

2. 2

   P. Gupta, N. Jagya, S. B. Pabhu, H. Durgapal, S. K. Acharya, S. K. Panda. (2012) Immunohistochemistry for the diagnosis of hepatitis E virus infection. Journal of Viral Hepatitis 19:2, e177-e183
   CrossRef

3. 3

   R Jardi, M Crespo, M Homs, E Eyden, R Girones, J Rodriguez-, A Caballero, M Buti, R Esteban, F Rodriguez-Frias. (2012) HIV, HEV and cirrhosis: evidence of a possible link from eastern Spain. HIV Medicinen/a-n/a
   CrossRef

4. 4

   Sarah Maylin, Robin Stephan, Jean-Michel Molina, Marie-Noelle Peraldi, Catherine Scieux, Elisabeth Nicand, François Simon, Constance Delaugerre. (2012) Prevalence of antibodies and RNA genome of hepatitis E virus in a cohort of French immunocompromised. Journal of Clinical Virology
   CrossRef

5. 5

   S.K. Sarin, Manoj Kumar. 2012. Hepatitis E. , 605-628.
   CrossRef

6. 6

   Marie-Louise Vachon, Ponni Perumalswami, Douglas T. Dieterich. 2011. Hepatobiliary Manifestations of Human Immunodeficiency Virus. , 1060-1082.
   CrossRef

7. 7

   K. Matsubayashi, H. Sakata, H. Ikeda. (2011) Hepatitis E virus infection and blood transfusion in Japan. ISBT Science Series 6:2, 344-349
   CrossRef

8. 8

   Irene Cacciola, Federica Messineo, Bruno Cacopardo, Vito Di Marco, Claudio Galli, Giovanni Squadrito, Cristina Musolino, Carlo Saitta, Teresa Pollicino, Giovanni Raimondo. (2011) Hepatitis E virus infection as a cause of acute hepatitis in Southern Italy. Digestive and Liver Disease 43:12, 996-1000
   CrossRef

9. 9

   Rakesh Aggarwal, Shahid Jameel. (2011) Hepatitis E. Hepatology 54:6, 2218-2226
   CrossRef

10. 10

    Kenrad E Nelson, Brittany Kmush, Alain B Labrique. (2011) The epidemiology of hepatitis E virus infections in developed countries and among immunocompromised patients. Expert Review of Anti-infective Therapy 9:12, 1133-1148
    CrossRef

11. 11

    Gurmit K. Jagjit Singh, Samreen Ijaz, Neesha Rockwood, Simon P. Farnworth, Emma Devitt, Mark Atkins, Richard Tedder, Mark Nelson. (2011) Chronic Hepatitis E as a cause for cryptogenic cirrhosis in HIV. Journal of Infection
    CrossRef

12. 12

    C. Koenecke, S. Pischke, A. Heim, L. Raggub, B. Bremer, R. Raupach, S. Buchholz, T. Schulz, M.P. Manns, A. Ganser, H. Wedemeyer. (2011) Chronic hepatitis E in hematopoietic stem cell transplant patients in a low-endemic country?. Transplant Infectious Diseasen/a-n/a
    CrossRef

13. 13

    Hideyuki Takahashi, Toshinori Tanaka, Suljid Jirintai, Shigeo Nagashima, Masaharu Takahashi, Tsutomu Nishizawa, Hitoshi Mizuo, Yasuyuki Yazaki, Hiroaki Okamoto. (2011) A549 and PLC/PRF/5 cells can support the efficient propagation of swine and wild boar hepatitis E virus (HEV) strains: demonstration of HEV infectivity of porcine liver sold as food. Archives of Virology
    CrossRef

14. 14

    Harry R. Dalton, Richard P. Bendall, Mo Rashid, Vic Ellis, Rachel Ali, Rene Ramnarace, William Stableforth, William Headdon, Rose Abbott, Cara McLaughlin, Emma Froment, Katie J. Hall, Nick P. Michell, Peter Thatcher, William E. Henley. (2011) Host risk factors and autochthonous hepatitis E infection. European Journal of Gastroenterology & Hepatology 23:12, 1200-1205
    CrossRef

15. 15

    Tatsuo Miyamura. (2011) Hepatitis E virus infection in developed countries. Virus Research 161:1, 40-46
    CrossRef

16. 16

    Mamadou Kaba, Hervé Richet, Isabelle Ravaux, Jacques Moreau, Isabelle Poizot-Martin, Anne Motte, Corinne Nicolino-Brunet, Françoise Dignat-George, Amélie Ménard, Catherine Dhiver, Philippe Brouqui, Philippe Colson. (2011) Hepatitis E virus infection in patients infected with the human immunodeficiency virus. Journal of Medical Virology 83:10, 1704-1716
    CrossRef

17. 17

    Rakesh Aggarwal. (2011) Clinical presentation of hepatitis E. Virus Research 161:1, 15-22
    CrossRef

18. 18

    Michael A. Purdy, Yury E. Khudyakov. (2011) The molecular epidemiology of hepatitis E virus infection. Virus Research 161:1, 31-39
    CrossRef

19. 19

    S. Ijaz, R. Szypulska, K. I. Tettmar, A. Kitchen, R. S. Tedder. (2011) Detection of hepatitis E virus RNA in plasma mini-pools from blood donors in England. Vox Sanguinisno-no
    CrossRef

20. 20

    D. Halleux, N. Kanaan, B. Kabamba, I. Thomas, Z. Hassoun. (2011) Hepatitis E virus: an underdiagnosed cause of chronic hepatitis in renal transplant recipients. Transplant Infectious Diseasen/a-n/a
    CrossRef

21. 21

    FE Keane, M Gompels, RP Bendall, R Drayton, L Jennings, J Black, G Baragwanath, NX Lin, WE Henley, S-L Ngui, S Ijaz, HR Dalton. (2011) Hepatitis E virus coinfection in patients with HIV infection. HIV Medicineno-no
    CrossRef

22. 22

    H. Zhang, U. Mohn, J.R. Prickett, S. Schalk, M. Motz, P.G. Halbur, A.R. Feagins, X.J. Meng, T. Opriessnig. (2011) Differences in capabilities of different enzyme immunoassays to detect anti-hepatitis E virus immunoglobulin G in pigs infected experimentally with hepatitis E virus genotype 3 or 4 and in pigs with unknown exposure. Journal of Virological Methods 175:2, 156-162
    CrossRef

23. 23

    S. B. Prabhu, P. Gupta, H. Durgapal, S. Rath, S. D. Gupta, S. K. Acharya, S. K. Panda. (2011) Study of cellular immune response against Hepatitis E Virus (HEV). Journal of Viral Hepatitis 18:8, 587-594
    CrossRef

24. 24

    Ana Isabel González Tallón, Víctor Moreira Vicente, María Luisa Mateos Lindemann, Linette María Achécar Justo. (2011) Hepatitis crónica E en paciente inmunocompetente. Gastroenterología y Hepatología 34:6, 398-400
    CrossRef

25. 25

    Joseph Torresi, Douglas Johnson. (2011) Hepatitis A and E Infection in International Travellers. Current Infectious Disease Reports 13:3, 248-255
    CrossRef

26. 26

    Nassim Kamar, Cyril Garrouste, Elizabeth B. Haagsma, Valérie Garrigue, Sven Pischke, Cécile Chauvet, Jérome Dumortier, Amélie Cannesson, Elisabeth Cassuto–Viguier, Eric Thervet, Filomena Conti, Pascal Lebray, Harry R. Dalton, Robert Santella, Nada Kanaan, Marie Essig, Christiane Mousson, Sylvie Radenne, Anne Marie Roque–Afonso, Jacques Izopet, Lionel Rostaing. (2011) Factors Associated With Chronic Hepatitis in Patients With Hepatitis E Virus Infection Who Have Received Solid Organ Transplants. Gastroenterology 140:5, 1481-1489
    CrossRef

27. 27

    M. A. Beale, K. Tettmar, R. Szypulska, R. S. Tedder, S. Ijaz. (2011) Is there evidence of recent hepatitis E virus infection in English and North Welsh blood donors?. Vox Sanguinis 100:3, 340-342
    CrossRef

28. 28

    Ana Isabel González Tallón, Víctor Moreira Vicente, María Luisa Mateos Lindemann. (2011) Hepatitis crónica E. Medicina Clínica
    CrossRef

29. 29

    M. Cornberg, M.P. Manns. (2011) Prävention der Virushepatitis A bis E. Der Internist 52:3, 250-264
    CrossRef

30. 30

    P. Colson, C. Dhiver, I. Poizot-Martin, C. Tamalet, R. Gérolami. (2011) Acute and chronic hepatitis E in patients infected with human immunodeficiency virus. Journal of Viral Hepatitis 18:3, 227-228
    CrossRef

31. 31

    P. Shukla, H. T. Nguyen, U. Torian, R. E. Engle, K. Faulk, H. R. Dalton, R. P. Bendall, F. E. Keane, R. H. Purcell, S. U. Emerson. (2011) Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant. Proceedings of the National Academy of Sciences 108:6, 2438-2443
    CrossRef

32. 32

    Sook-Hyang Jeong. (2011) Current Status of Hepatitis E Virus Infection in Korea. Gut and Liver 5:4, 427
    CrossRef

33. 33

    Amit Goel, Rakesh Aggarwal. (2011) Prevention of hepatitis E: another step forward. Future Microbiology 6:1, 23-27
    CrossRef

34. 34

    Pierre Sellier, Marie-Christine Mazeron, Sophie Tesse, Esma Badsi, John Evans, Jean-Dominique Magnier, Marie-Jose Sanson-Le-Pors, Jean-François Bergmann, Elisabeth Nicand. (2011) Hepatitis E Virus infection in HIV-infected patients with elevated serum transaminases levels. Virology Journal 8:1, 171
    CrossRef

35. 35

    Janick Selves, Nassim Kamar, Jean-Michel Mansuy, Jean-Marie Péron. (2010) Les hépatites virales E : une maladie émergente en France. Annales de Pathologie 30:6, 432-438
    CrossRef

36. 36

    Nassim Kamar, Lionel Rostaing, Florence Abravanel, Cyril Garrouste, Sebastien Lhomme, Laure Esposito, Grégoire Basse, Olivier Cointault, David Ribes, Marie Béatrice Nogier, Laurent Alric, Jean Marie Peron, Jacques Izopet. (2010) Ribavirin Therapy Inhibits Viral Replication on Patients With Chronic Hepatitis E Virus Infection. Gastroenterology 139:5, 1612-1618
    CrossRef

37. 37

    Jeff Turner, Andrew Godkin, Peter Neville, Jerry Kingham, Chin Lye Ch'ng. (2010) Clinical characteristics of hepatitis E in a “Non-Endemic” population. Journal of Medical Virology 82:11, 1899-1902
    CrossRef

38. 38

    Nicole Pavio, Jean-Michel Mansuy. (2010) Hepatitis E in high-income countries. Current Opinion in Infectious Diseases 23:5, 521-527
    CrossRef

39. 39

    Feng-Cai Zhu, Jun Zhang, Xue-Feng Zhang, Cheng Zhou, Zhong-Ze Wang, Shou-Jie Huang, Hua Wang, Chang-Lin Yang, Han-Min Jiang, Jia-Ping Cai, Yi-Jun Wang, Xing Ai, Yue-Mei Hu, Quan Tang, Xin Yao, Qiang Yan, Yang-Ling Xian, Ting Wu, Yi-Min Li, Ji Miao, Mun-Hon Ng, James Wai-Kuo Shih, Ning-Shao Xia. (2010) Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. The Lancet 376:9744, 895-902
    CrossRef

40. 40

    N. Kamar, F. Abravanel, C. Garrouste, I. Cardeau-Desangles, J. M. Mansuy, H. Weclawiak, J. Izopet, L. Rostaing. (2010) Three-month pegylated interferon-alpha-2a therapy for chronic hepatitis E virus infection in a haemodialysis patient. Nephrology Dialysis Transplantation 25:8, 2792-2795
    CrossRef

41. 41

    Christophe Renou, Alain Lafeuillade, Jean-François Cadranel, Nicole Pavio, Alexandre Pariente, Thierry Allègre, Cécile Poggi, Guillaume Pénaranda, François Cordier, Elisabeth Nicand. (2010) Hepatitis E virus in HIV-infected patients. AIDS 24:10, 1493-1499
    CrossRef

42. 42

    N. Kamar, J. Izopet, P. Cintas, C. Garrouste, E. Uro-Coste, O. Cointault, L. Rostaing. (2010) Hepatitis E Virus-Induced Neurological Symptoms in a Kidney-Transplant Patient with Chronic Hepatitis. American Journal of Transplantation 10:5, 1321-1324
    CrossRef

43. 43

    Amit Kumar, Subrat Kumar Panda, Hemlata Durgapal, Subrat Kumar Acharya, Shagufta Rehman, Upendra K. Kar. (2010) Inhibition of Hepatitis E virus replication using short hairpin RNA (shRNA). Antiviral Research 85:3, 541-550
    CrossRef

44. 44

    C. G. Teo. (2010) Much meat, much malady: changing perceptions of the epidemiology of hepatitis E. Clinical Microbiology and Infection 16:1, 24-32
    CrossRef